A new study suggests that epigenetic changes can alter the abundance of specific channels to control neuronal excitability, which is known to be dysregulated in many brain disorders.
The findings in cultured neurons hint that epigenetic drugs may be used to manipulate neuronal excitability, or signaling, in epilepsy, nerve pain, Alzheimer's disease, depression, drug addiction, and other diseases. Epigenetic changes such as DNA methylation contribute to neuronal plasticity critical to learning and memory, but matching epigenetic changes to specific genes that mediate the epigenetic effects on neuronal plasticity has remained challenging.
Studying rat cortical neurons in culture, Jarrod Meadows and colleagues found that dynamic DNA methylation plays a key role in setting the threshold for the excitability, or responsiveness, of the neuronal membrane. Blocking an enzyme that kick-starts DNA methylation made neurons even more responsive and likely to fire in r esponse to a given stimulus. DNA methylation curbed the expression of genes encoding a family of potassium channels that fine-tune the excitability of the neurons.
The researchers say that a better understanding of how epigenetics shapes neuronal excitability could guide the use of epigenetic drugs for neuropsychiatric and neurological disorders.
Article: Dynamic DNA methylation regulates neuronal intrinsic membrane excitability, Jarrod P. Meadows, Mikael C. Guzman-Karlsson, Scott Phillips, Jordan A. Brown, Sarah K. Strange, J. David Sweatt, John J. Hablitz, Science Signallng, doi: 10.1126/scisignal.aaf5642, published online 23 August 2016.